Epidemiology Program

Molecular Epidemiology of Lung Cancer

PI: Chu Chen PhD

Tobacco smoke is the major cause of lung cancer, the most common type of fatal cancer worldwide. A possible means by which tobacco smoke exerts its carcinogenic effect is the DNA damage produced by the generation of reactive oxygen species and the formation of DNA adducts. Since the majority of persons who smoke tobacco do not develop lung cancer, it is possible that those who do develop this disease have a relatively poor capacity to repair the DNA damage that results from smoking.

In a nested case-control study, we are in the process of determining whether polymorphisms of enzymes involved in the repair of smoking-induced DNA damage, namely those from the base excision (BER) and nucleotide excision repair (NER) pathways, are associated with risk of lung cancer. We genotype the functional single nucleotide polymorphisms (SNPs) as well as tagging SNPs of DNA repair genes. The lung cancer cases (n = 900) and controls (n = 1800) come from the participants in the Carotene and Retinol Efficacy Trial (CARET) of lung cancer prevention. Cases and controls will be compared with respect to the prevalence of putative "high risk" genotypes, alone and in combination with other putative "high risk" genotypes within each pathway and in the two pathways combined. Analyses will also examine whether inferred haplotypes and their combinations are associated with risk. We will assess whether associations differ by histologic subtypes and sex. The study has sufficient statistical power to identify interactions between some of the high-risk genotypes/haplotypes, and to investigate whether the risk associated with a particular genotype/haplotype varies by other risk factors, such as smoking intensity and recency, and dietary factors, such as intake of antioxidant-rich fruits and vegetables, and food-derived nutrients.

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